DESCRIPTION This study will explicitly compare the effects of a 12-week progressive exercise training program on 1) the clinical symptoms of chronic pain and PTSD, 2) pain threshold and tolerance, and 3) anti-stress, anti- nociceptive neurohormones such as neuropeptide Y (NPY) and allopregnanolone/pregnanolone (ALLO) in veterans with chronic pain/PTSD compared to healthy comparison participants. The revised study design includes a baseline cardiopulmonary exercise assessment (CPX) that will inform the exercise prescription for a 12-week progressive exercise training program, comprised of three 30-45 minute exercise sessions per week (walking or running, depending on the ability/capacity of the participant). Exercise sessions will be initially supervised by an exercise physiologist in the Clinical Studies Unit (CSU) at the VA Boston Healthcare System and then each participant will transition into the home. Weekly telephone calls by the PI will provide additional motivational support and assistance with problem solving. Implementation of the prescribed exercise regimen will also be supported by the use of heart rate and actigraph monitors programmed for the participant to achieve their prescribed heart rate range (HRR). Finally, an endpoint maximum load exercise assessment will occur at week 13 in order to track measurable change for both psychological and neurobiological factors and to delineate their impact on pain indices and PTSD symptomatology. Both maximum load exercise tests will be performed in accordance with guidelines published by the American College of Cardiology. Measures of pain, pain tolerance (via the cold pressor test) will be implemented 30 minutes before and 30 minutes after exercise testing as well as at a midpoint check-in at which self-report questionnaires will also be repeated. Based on the PI's earlier research, the role of exercise motivation and self-efficacy on changes in perceived pain and pain tolerance will be correlated with changes in NPY and ALLO levels, pre and post exercise. It is anticipated that differences in biological responses to aerobic and anaerobic exercise between healthy participants and those with chronic pain/PTSD will predict differences in the psychological and pain-reducing benefits of aerobic and anaerobic exercise. Once identified, such factors could be augmented by modification of the exercise regimen in order to help enhance the ant-stress hormone levels for the pain/PTSD population and experience clinically significant reductions in their symptoms. In order to obtain sufficient power as well as accounting for an expected drop-out rate of 18-20%, the proposed recruitment is 30 participants per condition (total of 60 participants). Data from this pilot work will be used to compute effect sizes in support of a future clinical trial incorporating individually prescribed exercise regimens and a motivationally based exercise behavior change intervention aimed at reducing pain and PTSD symptoms in our Veterans. Advanced education and training is sought by this CDA-2 award applicant in four broad areas: 1) psychophysiology of chronic pain and PTSD with a sub-focus on sex differences, 2) the neurobiology of chronic stress, PTSD, and pain, 3) exercise physiology and 4) the neuropsychology and neurobiology of traumatic brain injury (TBI). The combination of didactic and experiential training in these areas will serve the PI's long-term goal of becoming an independent scientist/practitioner in the VA focused on development of improved treatments for health conditions co-morbid with PTSD such as chronic pain and mild TBI. In the shorter-term, this CDA-2 will allow the PI to develop a more effective, motivationally based, exercise behavior change protocol that fosters long- term exercise compliance in patients with chronic pain/PTSD. This intervention will be used as an adjunct to cognitive interventions for these disorders to be further developed and studied via a larger VA, NIH, or DOD- funded grant for which the PI will apply in years 4-5 of the CDA2.